Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model

被引：46
作者：
Banerjee, Antara [1 ,2 ]
Bhattacharya, Parna [1 ]
Dagur, Pradeep K. [3 ]
Karmakar, Subir [1 ]
Ismail, Nevien [1 ]
Joshi, Amritanshu B. [1 ]
Akue, Adovi D. [4 ]
KuKuruga, Mark [4 ]
McCoy, John Philip, Jr. [3 ]
Dey, Ranadhir [1 ]
Nakhasi, Hira L. [1 ]
机构：
[1] US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA
[2] Bangabasi Coll, Dept Zool, Kolkata 700016, W Bengal, India
[3] NHLBI, Flow Cytometry Core, NIH, Bldg 10, Bethesda, MD 20892 USA
[4] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA
来源：
JOURNAL OF IMMUNOLOGY | 2018年 / 200卷 / 01期
关键词：
CD8; T-CELLS; GRANULOMATOUS INFLAMMATION; SUCCESSFUL THERAPY; DENDRITIC CELLS; INNATE IMMUNITY; HELPER-CELLS; IL-17; PROTECTION; VACCINATION; EXPRESSION;
D O I：
10.4049/jimmunol.1700674
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene-deleted Leishmania donovani (LdCen(-/-)) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in LdCen(-/-) -induced host protection in mice. Our results showed that compared with wild-type L. donovani infection, LdCen(-/-) parasites induce significantly higher expression of Th17 differentiation cytokines in splenic dendritic cells. There was also induction of IL-17 and its promoting cytokines in total splenocytes and in both CD4 and CD8 T cells following immunization with LdCen(-/-). Upon challenge with wild-type parasites, IL-17 and its differentiating cytokines were significantly higher in LdCen(-/-) -immunized mice compared with nonimmunized mice that resulted in parasite control. Alongside IL-17 induction, we observed induction of IFN-gamma-producing Th1 cells as reported earlier. However, Th17 cells are generated before Th1 cells. Neutralization of either IL-17 or IFN-gamma abrogated LdCen(-/-) -induced host protection further confirming the essential role of Th17 along with Th1 cytokines in host protection. Treatment with recombinant IL-23, which is required for stabilization and maintenance of IL-17, heightened Th17, and Tc17 responses in immunized mice splenocytes. In contrast, Th17 response was absent in immunized IL-23R(-/-) mice that failed to induce protection upon virulent Leishmania challenge suggesting that IL-23 plays an essential role in IL-17-mediated protection by LdCen(-/-) parasites. This study unveiled the role of IL-23-dependent IL-17 induction in LdCen(-/-) parasite-induced immunity and subsequent protection against visceral leishmaniasis.
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页码：163 / 176
页数：14
相关论文
共 82 条
[1]   Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[2]   IL-17-Expressing CD4+ and CD8+ T Lymphocytes in Human Toxoplasmosis [J].
Alves Silva, Jessica Liver ;
Rezende-Oliveira, Karine ;
da Silva, Marcos Vinicius ;
Gomez-Hernandez, Cesar ;
Peghini, Bethanea Crema ;
Silva, Neide Maria ;
Mineo, Jose Roberto ;
Rodrigues Junior, Virmondes .
MEDIATORS OF INFLAMMATION, 2014, 2014
[3]   IL-27 and IL-21 Are Associated with T Cell IL-10 Responses in Human Visceral Leishmaniasis [J].
Ansari, Nasim Akhtar ;
Kumar, Rajiv ;
Gautam, Shalini ;
Nylen, Susanne ;
Singh, Om Prakash ;
Sundar, Shyam ;
Sacks, David .
JOURNAL OF IMMUNOLOGY, 2011, 186 (07) :3977-3985
[4]   An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets [J].
Arora, Pooja ;
Porcelli, Steven A. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2016, (110)
[5]   Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs [J].
Avishek, Kumar ;
Kaushal, Himanshu ;
Gannavaram, Sreenivas ;
Dey, Ranadhir ;
Selvapandiyan, Angamuthu ;
Ramesh, V. ;
Negi, Narender Singh ;
Dubey, Uma S. ;
Nakhasi, Hira L. ;
Salotra, Poonam .
SCIENTIFIC REPORTS, 2016, 6
[6]   IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function [J].
Bai, Hong ;
Cheng, Jianjun ;
Gao, Xiaoling ;
Joyee, Antony George ;
Fan, Yijun ;
Wang, Shuhe ;
Jiao, Lei ;
Yao, Zhi ;
Yang, Xi .
JOURNAL OF IMMUNOLOGY, 2009, 183 (09) :5886-5895
[7]   Role of pro-inflammatory cytokine IL-17 in Leishmania pathogenesis and in protective immunity by Leishmania vaccines [J].
Banerjee, Antara ;
Bhattacharya, Parna ;
Joshi, Amritanshu B. ;
Ismail, Nevien ;
Dey, Ranadhir ;
Nakhasi, Hira L. .
CELLULAR IMMUNOLOGY, 2016, 309 :37-41
[8]   Induction and effector functions of TH17 cells [J].
Bettelli, Estelle ;
Korn, Thomas ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE, 2008, 453 (7198) :1051-1057
[9]   Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice [J].
Bhattacharya, Parna ;
Dey, Ranadhir ;
Dagur, Pradeep K. ;
Kruhlak, Michael ;
Ismail, Nevien ;
Debrabant, Alain ;
Joshi, Amritanshu B. ;
Akue, Adovi ;
Kukuruga, Mark ;
Takeda, Kazuyo ;
Selvapandiyan, Angamuthu ;
McCoy, John Philip, Jr. ;
Nakhasi, Hira L. .
INFECTION AND IMMUNITY, 2015, 83 (10) :3800-3815
[10]   Pathways of Antigen Processing [J].
Blum, Janice S. ;
Wearsch, Pamela A. ;
Cresswell, Peter .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 31, 2013, 31 :443-473
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